This is true of humans as well -- there are plenty of programs that get interesting and clear results in Phase 2 (the dose ranging phase: essentially "what dosage is most efficacious") that die in Phase 3 (roughly: "OK, how does that dose really work on a statistically significant population that also represents the demographics of the country"). These studies are so expensive that nobody goes into Phase 3 unless they believe Phase 2 pretty certainly demonstrated that the drug works, and well.
It's also hard to figure out just how the animal's hearing is improving (you can't simply ask). I'm sure they have some experiments, but growing the hairs back may be necessary but not sufficient. Look at all those Alzheimers programs aimed at removing the plaque that haven't demonstrated any value in the clinic. The plaque might not even be alzheimers itself -- it could merely be the body's response to some different underlying effect of the disease.
The choice of animal is very important, and the FDA cares a lot. Mice are popular because they are cheap. I worked on a program years ago that used guinea pigs because mice couldn't get the disease. We didn't use rats as the compound caused cancer in rats, and someone else had had their program derailed because the FDA required a separate analysis and study to demonstrate that the cancer was specific to rats and not other species (rats get lots of cancers). For our program the FDA required some studies in (non-guinea) pigs before they were willing to allow any human trials.
It's also hard to figure out just how the
animal's hearing is improving (you can't simply ask)
Oversimplification obviously, and "easy" is extreme relative to all the other hard parts involved but that part seems very doable
Essentially it's fractally complex.
There are various ways to measure these thing in animals and humans physiologically (ABRs, otoacoustic emissions, invasive and noninvasive electrophysiology), and with careful psychophysical experiments. None are perfect or comprehensive. Each method has its own strengths and weaknesses.
But it is indeed more complex than just testing a basic audibility threshold. The same issues come up with audigorams for hearing aid calibration and hearing in noise.
For that kind of thing, we're going to need real people who can communicate in detail.
"Rotating your eyeball" as a treatment for macular degeneration is a good example. Your brain needs a week or so to "reorient" even though the physical procedure is done in a couple hours.
Seems simpler than training a significant amount of them!
“How Loud Can Sound Physically Get?” - amazing breakdown of the subjective nature of loudness.
Basically, if we can regrow them, there’s a good chance of restoring hearing, provided the rest of the auditory system hasn’t atrophied too badly.
I hear a permanent and constant low-volume very high pitch "squeal" in my ears at all times,
I was never a big loud music listener, and I have always brought ear-plugs to loud events - and have had no big ear-rupturing moments (such as a gun firing close to my head without protection etc...
In the spirit of "there's a forum for everything," you can get help programming them yourself here:
But, I also enjoy being in silence.
Silence arrested by tinnitus.
I would enjoy a more meditative state... yet, tinnitus.
(Yes, I have tried "meditating it away")
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Aside: I love you.
Manganese could also play a part because its the most abundant metal in hair samples which might translate to the hairs in the ear. However to get it there, you'll need to increase your cysteine intake, but we dont absorb it easily through the gut so we have to use N Acetyl Cysteine...
SO many chemical variables....
Acetaminophen doesn't have the same problem for me so I'm assuming it's not just that I'm clenching my jaw without noticing.
The only tip I can give you is to always have some kind of background sound that you can focus on rather than the buzzing in your own head.
Also, avoid earplugs and headphones, they just create a wierd feedback loop.
A couple of the things I used to tell myself when it troubled me more than it does now:
- There's nothing you can do about this, so just forget about it.
- We all accumulate damage as we age. None of us are going into the grave in prime condition and if we do, that's a mark of a life not well-lived.
- The fact I can hear this noise means I'm alive: "I hear ringing, therefore I am".
These may not be helpful to you, so invent your own!
The other thing I would recommend is getting a hearing test. If it turns out you have hearing loss, then treatment for that (e.g. hearing aids) may reduce your tinnitus (one theory is that tinnitus is caused by your brain "turning up the gain" on your "audio inputs", so that when you have a hearing aid, your brain no longer needs to do that, and your tinnitus diminishes).
If it turns out you don't have hearing loss, then you can reassure yourself that your tinnitus is not a sign of any damage. I had always assumed my tinnitus was the result of damage due to a lot of music events but it turns out I have excellent hearing, which helps me ignore my tinnitus, because I no longer view it as proof that I hurt myself.
You may also notice that certain things make your tinnitus worse. For instance, if I have a few drinks, mine gets noticeably louder. But because I know the alcohol will wear off, I just ignore it because it's temporary.
It depends. My friend had a bad tinitus for years. He thought it was from clubbing and the jet noise in the military.
He just has bad hearing and with his hearing aids, the tinitus is gone.
I personally think this is great advice. I just imagine that the noise is the firing of my synapses.
With that said, my advice to you is, don’t do that. ;) Maybe you have it, maybe you don’t, so probably best to just ignore it, because it’s not a problem unless you start paying attention to it.
Interestingly, having this conversation on HN has made mine more noticeable, so, I better move on too!
You might want to experiment with changing your diet, drinking more water, etc.
I do eat a lot of sodium, but here is an interesting anecdote:
A friend's husband had Lyme Disease - and had very bad veritgo from it which was exacerbated by a high sodium intake (I assume the ear works on the sodium potassium pump in some manner?)
but she used to have to make a very careful diet for him so as to remove sodium as much as possible, which would prevent his vertigo.
"Where an inflammatory component is suspected in bilateral Ménière’s disease, short courses of systemic glucocorticoids may be appropriate. It recently has been shown that glucocorticoids not only influence inflammatory process in Ménière’s disease, but also alter fluid dynamics via an interaction with the sodium pumps in the semicircular canals (Ponduglula et al 2004). Intra-tympanic application of corticosteroids appears to have only temporary effects (Dodson 2004) and is probably not recommended"
The trials preceding the Phase IIa results were all extremely promising, and even the Phase IIa one showed statistically significant effect on a sound discrimination, which many long time hearing sufferers can tell you is even more frustrating a problem than the inability to perceive sound.
Biomedical research stocks are inherently risky. I could be deluding myself, but my lay reading of the research, and as someone who has suffered from tinnitus for a long time brought on my noise overexposure, I think there is a very promising shot at this drug. Maybe FREQ will not be the ones to realize it and some other company will take the patent into real life clinical medicine, and FREQ is certainly not the ONLY company pursuing this angle. But their successes so far have kept me holding the stock, and I keep buying more.
Interesting approach, I'd love to see it work. But given the mixed results plus the class action lawsuits that still seem unsettled (at least I didn't find any news), this doesn't really seem investable to me. Biotech startups are risky enough even without such problems.
What other companies are working on this problem?
The failure of the prior trial was suspected, and I believe it, due to a refractory response by overdosing the inner ear with too frequent administrations of the drug, and then testing for effect too soon. I bet even those candidates of the phase IIa trial though would, if checked on now, show some improvement.
Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real, we mammals just don't have the natural cellular signaling to redifferentiate those base cells - small molecule drugs like FX322 do exactly that. I am optimistic they'll eventually find the right dosing regimen to see reliable and optimal clinical effect, and it will be a seismic advance in medicine.